Recessive genetic diseases impose physical and psychological impacts to both newborns and parents who may not be aware of being carriers. Expanded carrier screening (ECS) allows screening for multiple genetic conditions at the same time. Whether or not such non-targeted panethnic approach of genetic carrier screening should replace the conventional targeted approach remains controversial. There is limited data on view and acceptance of ECS in general population, as well as the optimal timing of offering ECS to women. This study assesses views and acceptance of ECS in both pregnant women and non-pregnant women seeking fertility counseling or checkup and their reasons for accepting or declining ECS.
This is a questionnaire survey with ECS information in the form of pamphlets distributed from December 2016 to end of 2018. Women were recruited from the antenatal clinics and the assisted reproductive unit at the Department of Obstetrics and Gynaecology, Queen Mary Hospital and the prepregnancy counseling clinis it allows more reproductive options and may cause less anxiety. Nevertheless, implementation of universal panethnic ECS will need more patient education, ways to reduce anxiety, and consensus on optimal timing in offering ECS.
Our study demonstrates that expanded carrier screening was perceived as a better screening by most women. https://www.selleckchem.com/products/oss-128167.html Prepregnancy ECS maybe a better approach than ECS during pregnancy, as it allows more reproductive options and may cause less anxiety. Nevertheless, implementation of universal panethnic ECS will need more patient education, ways to reduce anxiety, and consensus on optimal timing in offering ECS.The NONO gene is located on chromosome Xq13.1 and encodes a nuclear protein involved in RNA synthesis, transcriptional regulation, and DNA repair. Hemizygous variants in NONO have been reported to cause mental retardation, X-linked, syndromic 34 (MRXS34) in males. Due to the scarcity of clinical reports, the clinical characteristics and mutation spectrum of NONO-related disorder have not been entirely determined.
We reported a fetus with hypoplastic left heart syndrome, performed a comprehensive genotyping examination, including copy-number variation sequencing and whole-exome sequencing, and screened for the genetic abnormality. We also conducted an mini-gene splicing assay to demonstrate the predicted deleterious effects of an intronic variant of NONO.
Exome sequencing identified a novel intronic variant (c.154 + 9A &gt; G) in intron 4 of the NONO gene (NM_001145408.1). It was predicted to insert 4 bp of intron 4 into the mature mRNA. Minigene assay revealed that the c.154 + 9A &gt; G variant caused the activation of the intronic cryptic splice site and 4 bp insertion (c.154_155ins GTGT) in mature mRNA. Literature review shows that cardiac phenotype, including left ventricular non-compaction cardiomyopathy and congenital heart disease, are consistent features of MRXS34.
This study enlarges the mutation spectrum of NONO, further expands hypoplastic left heart syndrome to the phenotype of MRXS34 and points out the importance of intronic sequence analysis and the need for integrative functional studies in the interpretation of sequence variants.
This study enlarges the mutation spectrum of NONO, further expands hypoplastic left heart syndrome to the phenotype of MRXS34 and points out the importance of intronic sequence analysis and the need for integrative functional studies in the interpretation of sequence variants.Pig is an important agricultural economic animal, providing large amount of meat products. With the development of functional genomics and bioinformatics, lots of genes and functional single nucleotide polymorphisms (SNPs) related to disease resistance and (or) economic traits in pigs have been identified, which provides the targets for genetic improvement by genome editing. Base editors (BEs), combining Cas9 nickase and cytidine or adenine deaminase, achieve all four possible transition mutations (C-to-T, A-to-G, T-to-C, and G-to-A) efficiently and accurately without double strand breaks (DSBs) under the protospacer adjacent motif (PAM) sequence of NGG. However, the NGG PAM in canonical CRISPR-Cas9 can only cover approximately 8.27% in the whole genome which limits its broad application. In the current study, hA3A-BE3-NG system was constructed with the fusion of SpCas9-NG variant and hA3A-BE3 to create C-to-T conversion at NGN PAM sites efficiently. The editing efficiency and scope of hA3A-BE3-NG were confirmed in HEK293T cells and porcine fetal fibroblast (PFF) cells. Results showed that the efficiency of hA3A-BE3-NG was much higher than that of hA3A-BE3 on NGH (H = A, C, or T) PAM sites (21.27 vs. 2.81% at average). Further, nonsense and missense mutations were introduced efficiently and precisely via hA3A-BE3-NG in multiple pig economic trait-related genes (CD163, APN, MSTN, and MC4R) in PFF cells by one transfection. The current work indicates the potential applications of hA3A-BE3-NG for pyramid breeding studies in livestock.Ovarian aging leads to reproductive and endocrine dysfunction, causing the disorder of multiple organs in the body and even declined quality of offspring's health. However, few studies have investigated the changes in gene expression profile in the ovarian aging process. Here, we applied integrated bioinformatics to screen, identify, and validate the critical pathogenic genes involved in ovarian aging and uncover potential molecular mechanisms. The expression profiles of GSE84078 were downloaded from the Gene Expression Omnibus (GEO) database, which included the data from ovarian samples of 10 normal C57BL/6 mice, including old (21-22 months old, ovarian failure period) and young (5-6 months old, reproductive bloom period) ovaries. First, we filtered 931 differentially expressed genes (DEGs), including 876 upregulated and 55 downregulated genes through comparison between ovarian expression data from old and young mice. Functional enrichment analysis showed that biological functions of DEGs were primarily immuovide effective molecular targets for the treatment of ovarian aging.